The objectives of this research proposal are to examine in a non-convergent manner the synthesis and attendant chemistry of the potent antitumor antibiotics esperamicin A2, calicheamicin, and neocarzinostatin chromophore A, (1, 2 and 3 respectively). The structural factors that influence their proposed biological mode of action will be examined. This involves examining the effect of substituent/structural effects upon the relative rate of 1,4-diyl formation.